Natamycin (syn. Pimaricin) is a polyene fungicide that is derived from the soil microorganisms, Streptomyces natalensis, Streptomyces lydicus, and Streptomyces chattanoogensis. It is commercially produced by fermenting and then lysing Streptomyces natalensis. Natamycin is commonly used to deter the growth of fungus on edible solid foods, however, due to its poor solubility in water, it is often difficult to use.
One way the solubility issue has been overcome in the past is by the use of a wettable powder. A wettable powder formulation is a dry, finely ground formulation. In this type of formulation, the active ingredient is combined with a finely ground dry carrier, usually a mineral clay, and with other ingredients that enhance the ability of the powder to be suspended in water. Upon mixing the wettable powder with water, a suspension is formed, which is then applied by a spray technique.
One disadvantage of wettable powders is that the spray liquid must be continuously mixed to prevent settling of insoluble materials. Another disadvantage is that wettable powders and soluble powder formulations tend to produce dust upon handling, such as when pouring, transferring or measuring them. This dust may pose health hazards. Further, powder formulations tend to wet poorly and also solubilize slowly upon addition to water. Powder formulations thus take longer to wet, disperse and solubilize in a tank-mix. Formation of lumps or partially solubilized spray solutions leads to uneven distribution of the natamycin in the tank-mix with the potential for reduced performance. Sometimes, foam in the spray tank caused by spray tank adjuvants can also affect wetting and solubility of wettable and soluble powders. Wettable powder formulations may also leave undesirable insoluble residues both in the tank and on materials in need of treatment.
For many years those of skill in the art have attempted to develop concentrated aqueous natamycin formulations. One challenge is that milling natamycin causes unacceptably high viscosity in most formulations. If natamycin is not milled, however, suspension concentrates are not stable because the natamycin settles out of the formulation. Yet another problem with natamycin formulations is that they are especially susceptible to bacterial growth.
U.S. Pat. No. 5,552,151 suggests natamycin formulations with up to 40% w/w natamycin. This patent fails to provide any formulation examples with such high concentrations of natamycin. Further, the patent states that the most preferred range of natamycin is from 5 to 20%. In addition, this patent fails to teach or suggest how to prevent the natamycin from settling out of a suspension concentrate formulation.
U.S. Pat. Nos. 6,291,436 and 6,576,617 disclose solid natamycin formulations with particles less than 9 microns in diameter. These patents, however, fail to teach or suggest how to overcome the viscosity issues associated with milled natamycin in liquid formulations.
DSM has successfully created suspension concentrate natamycin formulations with concentrations of up to 10% w/w of natamycin (i.e., Zivion A (˜4% SC), Zivion P (˜4% SC), Delvo® Coat L02101 (˜5% SC) and Delvocide L (˜10% SC), Delvo is a registered trademark of DSM). While these formulations are successful, there is a need in the art for more concentrated formulations. These formulations will allow for reduced shipping and handling costs.